Our overall objective is a better understanding of the effects of alcohol on liver and intestinal cells, using both acute and chronic alcohol models. These studies will be carried out in rat and man. When possible human liver cells will also be studied using tissue culture systems. Our studies are being done on human liver cells maintained and grown in two types of culture systems, namely, a monolayer and a perfusion system. We hope to demonstrate in these systems the concentrations of alcohol and the time needed to produce an increase in ethanol metabolism. At the same time we will examine the biochemical mechanisms involved. We will also be studying the agents which may accelerate the metabolism of alcohol such as alanine, glycolate, urate and artificial electron acceptors. Studies are also being directed to the mechanism of increased collagen deposition and fibrosis seen in alcoholic cirrhosis. We are studying the various steps in collagen synthesis and degradation in order to determine which or how many of the various critical biochemical steps are modified or influenced by alcohol administration. Based on a model using murine viral hepatitis we are also studying the effects of alcohol on viral hepatitis and conversely the effects of viral hepatitis on alcohol metabolism since these are clinically important areas. Having demonstrated the positive effect of insulin and glucagon on liver regeneration, we are examining the effects of these two hormones on reversing or modifying the adverse effects of alcohol on the liver. Finally, we are examing the effects of alcohol on intestinal transport using isolated intestinal cells and membrane vesicles derived from microvillus and basolateral membranes. These studies include the effects of alcohol on sugar and amino acid transport. BIBLIOGRAPHIC REFERENCES: Isselbacher, K.J. Metabolic and hepatic effects of alcohol. New Eng. J. Med. 296: 612, 1977. Isselbacher, K.J. and Feller, E.R. The natural history and management of alcoholic liver disease. In, Alcohol and the Liver. M.M. Fisher and J.G. Rankin, eds. New York, Plenum Press, 1977 (in press).